RESUMO
The host cellular environment is a key determinant of pathogen infectivity. Viral gene expression and viral particle production of glucose-6-phosphate dehydrogenase (G6PD)-deficient and G6PD-knockdown cells were much higher than their counterparts when human coronavirus (HCoV) 229E was applied at 0.1 multiplicity of infection. These phenomena were correlated with increased oxidant production. Accordingly, ectopic expression of G6PD in G6PD-deficient cells or addition of antioxidant (such as alpha-lipoic acid) to G6PD-knockdown cells attenuated the increased susceptibility to HCoV 229E infection. All experimental data indicated that oxidative stress in host cells is an important factor in HCoV 229E infectivity.
Assuntos
Resfriado Comum/virologia , Coronavirus Humano 229E/crescimento & desenvolvimento , Infecções por Coronavirus/enzimologia , Infecções por Coronavirus/virologia , Deficiência de Glucosefosfato Desidrogenase/virologia , Células Cultivadas , Resfriado Comum/enzimologia , Coronavirus Humano 229E/metabolismo , Fibroblastos/enzimologia , Fibroblastos/virologia , Glucosefosfato Desidrogenase/biossíntese , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Humanos , Estresse Oxidativo , Ácido Tióctico/metabolismo , Vírion/metabolismoRESUMO
Rhinovirus infections cause wheeze, cough, and bronchial hyperresponsiveness. To investigate the involvement of cysteinyl-leukotrienes and prostanoids in these symptoms, bronchial biopsy specimens from 9 normal subjects (nonatopic and with no history of chronic lung disease) were immunostained for 5-lipoxygenase (5-LO) and cyclooxygenase (COX) pathway enzymes 2 weeks before and 4 days after experimental infection with human rhinovirus serotype 16. 5-LO-positive cell counts increased 9-fold (from 0.48 to 4.4 cells/mm(2); P <.05), and 5-LO-activating protein (FLAP)-positive cell counts increased 3.6-fold (from 1.8 to 6.5 cells/mm(2); P =.09). Levels of leukotriene A(4) hydrolase and leukotriene C(4) synthase were unchanged. COX-2--positive cell counts increased from 0 to 2.6 cells/mm(2) (P =.009), with no change in COX-1 levels. Increases of 3-4-fold were seen in levels of macrophages (P =.02) and mast cells (P =.07) but not of eosinophils (P >.4), and bronchoalveolar lavage fluid cysteinyl-leukotriene levels doubled (from 11.2 to 20.4 pg/mL; P =.13). Cold symptom scores correlated with bronchial immunostaining for FLAP (rho = 0.93; P =.001). In normal subjects, rhinovirus colds induce bronchial inflammation with markedly enhanced expression of 5-LO pathway proteins and COX-2.
Assuntos
Araquidonato 5-Lipoxigenase/biossíntese , Brônquios/enzimologia , Resfriado Comum/enzimologia , Isoenzimas/biossíntese , Prostaglandina-Endoperóxido Sintases/biossíntese , Araquidonato 5-Lipoxigenase/análise , Biópsia , Brônquios/patologia , Resfriado Comum/tratamento farmacológico , Ciclo-Oxigenase 2 , Cisteína/análise , Humanos , Isoenzimas/análise , Leucotrienos/análise , Proteínas de Membrana , Prostaglandina-Endoperóxido Sintases/análiseRESUMO
Proteolytic activity and concentrations of serum protease inhibitors were measured in nasal secretions collected from 14 adult patients (6 males and 8 females) with common colds. Elastase concentration and fibrinolytic activity increased about three days after the onset of the colds, and there was a significant correlation between both values (p less than 0.01). Trypsin-like protease activity was very low. Of all serum protease inhibitors, inter-alpha-trypsin inhibitor could not be detected, and alpha 2-macroglobulin could be detected in only two cases. Variation of alpha 1-antitrypsin value was very similar to that of alpha 1-antichymotrypsin, and there was a significant correlation between alpha 1-antitrypsin and elastase (p less than 0.001). Phoretic patterns of crossed immuneelectrophoresis revealed the presence of alpha 1-antitrypsin-protease complex. alpha-protease inhibitors are major serum protease inhibitors in nasal secretions of persons with colds, and inhibit excess proteolytic activity of serine proteases. This protection is considered to be one of the major factors in preventing irreversible mucosal change.
Assuntos
Resfriado Comum/enzimologia , Endopeptidases/metabolismo , Muco/enzimologia , Mucosa Nasal/metabolismo , Inibidores de Proteases/metabolismo , Adulto , Catepsina B , Catepsinas/sangue , Catepsinas/metabolismo , Endopeptidases/sangue , Feminino , Fibrinolisina/sangue , Fibrinolisina/metabolismo , Humanos , Imunoeletroforese Bidimensional , Masculino , Elastase Pancreática/sangue , Elastase Pancreática/metabolismo , Inibidores de Proteases/sangueRESUMO
Associations have been found between self-reported cold symptoms and Pi type in 84 pairs of identical twins. The risk of cold symptoms relative to MM phenotypes was 1.2 times greater in MS and 2.5 times greater in MZ individuals. Up to 9% of variance in cold symptoms could be attributed to Pi type, representing at least 20% of the total genetical variance.